Replenishing the tumor microenvironment with new T cells
Kineta has developed a diverse set of anti-CD27 agonist antibodies. They are fully human monoclonal antibodies (mAbs) that demonstrate low nM binding affinity to CD27 in humans. In preclinical studies, Kineta’s selected lead anti-CD27 agonist mAbs induce T cell proliferation, NK activation and secretion of cytokines involved in T cell priming and recruitment, demonstrating the ability to potentiate new anti-tumor responses. Kineta is in the final stage of lead selection and plans to nominate a clinical candidate in mid-2022.
CD27 is a clinically validated drug target with a benign toxicology profile. It is a member of the TNF receptor superfamily and plays a critical role in T-cell activation by providing a co-stimulatory signal together with its ligand CD70. CD27 is highly expressed on naïve T cells and also provides a co-stimulatory signal for NK cell activation.
A major challenge in cancer immunotherapy is T cell “exhaustion”. Anti-cancer T cells, through repeated stimulation, begin to lose their cancer-fighting effector functions. We refer to these T cells as exhausted. Once a T cell is exhausted, further stimulation becomes impossible. CD27 agonist mAbs help the immune system to generate new and different populations of anticancer “memory” T cells from naïve T cells. They also reduce the number of Treg cells, which are a type of immune suppressing T cell. Finally, CD27 mAbs activate NK cells, a type of immune cell that can directly kill cancer cells. By these three mechanisms, CD27 mAbs inhibit tumor growth. Anti-CD27 agonist therapy has demonstrated efficacy as a monotherapy and in combination with other therapies in human clinical studies.
An estimated 19.3 M new cases of cancer were diagnosed with over 10 M deaths in 2020 worldwide. Cancer is now the second leading cause of death in the United States, second only to heart disease, with over 600,000 deaths in 2020. In 2021, roughly 1.9 M people will be diagnosed with cancer in the United States. Breast, lung, and colorectal cancers account for 50% of all new diagnoses in women while prostate, lung, and colorectal cancers account for 46% new diagnoses in men.1 The global market for immuno-oncology therapies totaled $30 B in 2020 and is forecast to grow to $95 B by 2026.2
Kineta is developing a novel anti-CD27 agonist monoclonal antibody that may be an effective immunotherapy for blood cancers including Hodgkin’s lymphoma and diffuse large B-cell lymphoma and solid tumors including renal cell carcinoma, ovarian and colorectal cancer. These initial target indications represent ~130,000 patients in the US annually and a significant medical need with a large worldwide commercial opportunity for this novel immunotherapy. 3
Thierry Guillaudeux, PhD, Vice President Immuno-oncology at Kineta; European Society for Medical Oncology (ESMO) Immuno-Oncology Congress 2021; Novel fully human agonist antibodies against the T-cell costimulatory receptor CD27shape adaptive anti-tumor immunity poster; December 8-11, 2021
Thierry Guillaudeux, PhD, Vice President Immuno-oncology at Kineta; Society for Immunotherapy of Cancer (SITC) 36th Anniversary Annual Meeting; A promising cancer immunotherapy target: Novel agonistic human antibodies against the human T-cell costimulatory receptor CD27 poster; November 13, 2021
Thierry Guillaudeux, PhD, Vice President Immuno-oncology at Kineta; Society for Immunotherapy of Cancer (SITC) 36th Anniversary Annual Meeting; A promising cancer immunotherapy target: Novel agonistic human antibody against the human T-cell costimulatory receptor CD27 poster; October 5-6, 2021
1. Rebecca L. Siegel et al.; Cancer statistics, 2020; ACS Journals; First published: 08 January 2020 https://doi.org/10.3322/caac.21660
2. GlobalData; Thematic Research: Immuno-Oncology Report, March 2021
3. GlobalData epidemiology forecasts for HL, DLBCL, RCC, OC, CRC